Single-Chain Variable Fragment Antibody of Vascular Cell Adhesion Molecule 1 as a Molecular Imaging Probe for Colitis Model Rabbit Investigation
Single-Chain Variable Fragment Antibody of Vascular Cell Adhesion Molecule 1 as a Molecular Imaging Probe for Colitis Model Rabbit Investigation
复制标题
血管细胞粘附分子1的单链可变片段抗体作为分子成像探针用于结肠炎模型兔研究
DOI：
10.1155/2019/2783519
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发表时间：
2019-01-01
影响因子：
--
通讯作者：
Lu, Diyu
中科院分区：
文献类型：
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作者：
Liu, Chunbao;Zhou, Jun;Lu, Diyu
血管细胞粘附分子-1（VCAM-1）由于在炎症发展中的关键作用，可能成为结肠炎研究的一个有前途的靶点。单链可变区抗体（Single-chain variable fragment，scFv）作为一种显像探针具有快速的血液清除特性。我们将Tc-99 m-scFv-VCAM-1探针应用于兔结肠炎模型，检测其显像性能。制备结肠炎模型兔，并在结肠中证实典型的炎性病变。合成Tc-99 m-scFv-VCAM-1探针，并在成像检查前注射到模型动物体内。闪烁成像在SPECT平面和SPECT/CT融合图像中均检测到结肠炎病变，模型组的靶/非靶比值（2.71 ± 0.31）高于对照组（1.12 ± 0.10）。生物分布研究确定了不同器官中的示踪剂摄取，放射自显影（ARG）证实了结肠病变中的探针蓄积。在ARG感兴趣区域的定量分析中，模型结肠与对照结肠的摄取比为4.71 +/-0.61。免疫印迹和免疫组化证实模型结肠中VCAM-1的表达较对照结肠中更强。我们的成像研究表明，scFv-VCAM-1分子成像是炎症性肠道疾病诊断和评估的一种有前途的方法。
Vascular cell adhesion molecule-1 (VCAM-1) can be a promising target for colitis study because of its critical role in inflammation development. Single-chain variable fragment (scFv) antibody presents fast blood clearance when served as an imaging probe. We applied the probe of Tc-99m-scFv-VCAM-1 to colitis rabbit to examine its imaging performance. The colitis model rabbit was prepared, and a typical inflammatory lesion was confirmed in the colon. The probe of Tc-99m-scFv-VCAM-1 was synthesized and injected into the model animal before imaging examination. Scintigraphy detected colitis lesions in both SPECT planar and SPECT/CT fused images, with higher target-to-nontarget ratios in the model group (2.71 +/- 0.31) than those in the control group (1.12 +/- 0.10). Biodistribution study determined tracer uptake in different organs, and autoradiography (ARG) confirmed probe accumulation in colon lesions. The uptake ratio of the model colon to the control colon was 4.71 +/- 0.61 in quantitative analysis of the ARG regions of interest. Stronger VCAM-1 expression in the model colon than that in the control colon was confirmed by western blotting and immunohistochemistry. Our imaging study indicates molecular imaging with scFv-VCAM-1 as a promising way for inflammatory bowel disease diagnosis and evaluation.